Despite the fact that hematoporphyrin derivative (HPD) is widely used in photodynamic therapy (PDT) for treating tumors, the precise chemical nature of the active ingredient remains undefined. We have recently obtained evidence indicating that dimeric and trimeric porphyrins connected via ester linkages may be the active component of HPD. This proposal focuses on (1) further characterization and verification of the structure of the active components of HPD by model studies; (2) rational synthesis of specific porphyrin dimers and analogs to improve the yield and purity of the active tumoricidal agent and to probe the structure/activity relationship for these type of compounds; (3) preparation of stable, active PDT drugs which possess enhanced light absorptivity in the long wavelength region to which tissues are transparent; and (4) set up photosensitization tests for screening synthetic HPD analogs. The promising drugs produced and screened in this program will be sent to Dr. David Kessel's laboratory at Wayne State University/Harper Hospital for additional tumor localization and pharmacokinetic studies. The ultimate goal is to produce a highly purified, more effective tumoricidal agent of known composition, thus replacing crude HPD for general clinical use.